tbuckley/cabot-search huggingface dataset:
Addition of Bevacizumab to Erlotinib as First-Line Treatment of Patients With EGFR-Mutated Advanced Nonsquamous NSCLC: The BEVERLY Multicenter Randomized Phase 3 Trial
Authors: Maria Carmela Piccirillo, Laura Bonanno, Marina Chiara Garassino, Giovanna Esposito, Claudio Dazzi, Luigi Cavanna, Marco Angelo Burgio, Francesco Rosetti, Simona Rizzato, Floriana Morgillo, Saverio Cinieri, Antonello Veccia, Maximilan Papi, Giuseppe Tonini, Vittorio Gebbia, Serena Ricciardi, Daniele Pozzessere, Alessandra Ferro, Claudia Proto, Raffaele Costanzo, Manolo D’Arcangelo, Manuela Proietto, Piera Gargiulo, Raimondo Di Liello, Laura Arenare, Filippo De Marinis, Lucio Crinò, Fortunato Ciardiello, Nicola Normanno, Ciro Gallo, Francesco Perrone, Cesare Gridelli, Alessandro Morabito
Journal: Journal of Thoracic Oncology (2022)

Adding bevacizumab to erlotinib prolonged progression-free survival (PFS) of patients with EGFR-mutated advanced NSCLC in the Japanese JO25567 trial, but limited data were available in non-Asian patients. BEVERLY is an Italian, multicenter, randomized, phase 3 investigating the addition of bevacizumab to erlotinib as first-line treatment of advanced EGFR-mutated NSCLC.Eligible patients were randomized 1:1 to erlotinib plus bevacizumab or erlotinib alone. Investigator-assessed PFS and blinded independent centrally reviewed PFS were coprimary end points. With 80% power in detecting a 0.60 hazard ratio and two-sided α error of 0.05, 126 events of 160 patients were needed. The trial was registered as NCT02633189 and EudraCT 2015-002235-17.From April 11, 2016, to February 27, 2019, a total of 160 patients were randomized to erlotinib plus bevacizumab (80) or erlotinib alone (80). At a median follow-up of 36.3 months, median investigator-assessed PFS was 15.4 months (95% confidence interval [CI]: 12.2-18.6) with erlotinib plus bevacizumab and 9.6 months (95% CI: 8.2-10.6) with erlotinib alone (hazard ratio = 0.66, 95% CI: 0.47-0.92). Blinded independent centrally reviewed PFS analysis confirmed this result. A statistically significant interaction with treatment effect was found for smoking habit (p = 0.0323), with PFS prolongation being clinically significant only among current or previous smokers. Hypertension (grade ≥3: 24% versus 5%), skin rash (grade ≥ 3: 31% versus 14%), thromboembolic events (any grade: 11% versus 4%), and proteinuria (any grade: 23% versus 6%) were more frequent with the combination.The addition of bevacizumab to first-line erlotinib prolonged PFS in Italian patients with EGFR-mutated NSCLC; toxicity was increased with the combination but without unexpected safety issues.
Body mass index, obesity and acute kidney injury after robot-assisted partial nephrectomy: Results from a high-volume robotic center
Authors: M. Paciotti, C.A. Bravi, A. Mottaran, L. Sarchi, P. Piazza, A. Martini, F. Gonzalez Meza, M.A. Corsetti, S. Knipper, M. Amato, R. Farinha, S. Puliatti, S. Scarcella, C. Sinatti, G. De Naeyer, R. De Groote, A. Mottrie
Journal: European Urology (2022)
Impact of establishing a precision oncology program at a rural academic cancer center on cancer care delivery.
Authors: Idona Brewer, Jacob Kettle, Alexander James Johnson, Venkata Vosuri, Tolga Tuncer, Christos N. Papageorgiou
Journal: Journal of Clinical Oncology (2022)

e18660 Background: The use of molecular profiling, biomarkers, and other targetable tumor alterations is becoming a central component of modern cancer care. Many oncologists use Next Generation Sequencing to guide treatment decisions. There are many challenges of implementing precision oncology through traditional clinical operations. The purpose of this project is to enhance patient care by establishing a new clinical program with the specific focus of advancing and expanding the utilization of precision oncology. Methods: The precision oncology program (POP) was designed as a consult service and functions to assist oncologists in appropriate testing, interpreting results, and identifying additional treatment options. After referral, the POP committee discusses each patient case and offers testing and/or therapeutic recommendations to the referring provider. POP predominantly focused on patients with unresectable or metastatic solid tumors that had relapsed after at least one line of standard of care therapy. The effect of the program will be measured by the volume of patient consults, the number and nature of recommendations from the consulting program, and the direct impact of recommendations on patient care. Results: There were approximately 323 new diagnoses of advanced stage solid tumors in 2021 at the Ellis Fischel Cancer Center (EFCC) at the University of Missouri-Columbia. There were 205 FoundationOne liquid and tissue Next Generation Sequencing (NGS) of solid tumors ordered since initiation of this service. Utilization of NGS testing has increased by 100% year-over-year from 2020 to 2021 since the implementation of this program. The impact of this program is reflected in the increased NGS testing for multiple malignancy types. Specifically, 34% more NGS tests in advanced lung cancers, 733% in breast, 60% in head and neck cancers, 166% colorectal and 500% in prostate cancer. Since the launch of POP in late 2020, we obtained consults on 46 patients. Additional biomarker testing was recommended for 39% of all consults, with a new actionable target being identified in 33% of patients. The amount of biomarker testing increased from averaging 6-7 tests per month to averaging 21 tests per month with an average number of 5 mutations per sample. Conclusions: The POP consult service has improved the testing and the identification of actionable mutations of patients at EFCC. The program has led to new treatment options in 33% of patients reviewed.
KRAS mutation in germ tumors with somatic transformation: Genetic pattern by FoundationOne CDx test
Authors: J.J. Cendejas Gomez, A. Scavuzzo, M.D. Perez Montiel, A. Quiroz Compean, J.S. Muruato Araiza, O.D. Victorio Vargas, N.J. Jimenez Guendulain, N. Sobrevilla Moreno, M.A. , Jimenez Rios
Journal: European Urology (2022)
RARE-04. Hypothalamic syndrome – severe sequelae due to different sellar and parasellar masses
Authors: Hermann L Müller
Journal: Neuro-Oncology (2022)

Abstract Hypothalamic syndrome is a rare disorder caused by disease- and/or treatment-related injury to the hypothalamus, most commonly associated with rare, noncancerous parasellar masses such as craniopharyngioma, germ cell tumours, gliomas, cysts of Rathke’s pouch and Langerhans cell histiocytosis as well as genetic neurodevelopmental syndromes such as Prader-Willi syndrome and septo-optic dysplasia. Hypothalamic syndrome is characterized by intractable weight gain associated with severe morbid obesity and memory impairment, attention deficit, reduced impulse control as well as increased risk of cardiovascular and metabolic disorders. Currently, there is no cure for this condition. Treatments used for general obesity such as surgery, medication and counselling are often tried in hypothalamic syndrome, but are mostly ineffective, and there are no medications specifically approved for hypothalamic syndrome. The most important aspects of presentation and outcome of hypothalamic syndrome due to different neuro oncological diseases, its risk factors and an overview of currently available therapeutic interventions aiming to decrease and ameliorate the consequences of hypothalamic dysfunction will be presented. Furthermore, novel aspects and perspectives for future research will be discussed.
Chronic Traumatic Encephalopathy in the Brains of Military Personnel
Authors: David S. Priemer, Diego Iacono, C. Harker Rhodes, Cara H. Olsen, Daniel P. Perl
Journal: New England Journal of Medicine (2022)

Persistent neuropsychiatric sequelae may develop in military personnel who are exposed to combat; such sequelae have been attributed in some cases to chronic traumatic encephalopathy (CTE). Only limited data regarding CTE in the brains of military service members are available.We performed neuropathological examinations for the presence of CTE in 225 consecutive brains from a brain bank dedicated to the study of deceased service members. In addition, we reviewed information obtained retrospectively regarding the decedents' histories of blast exposure, contact sports, other types of traumatic brain injury (TBI), and neuropsychiatric disorders.Neuropathological findings of CTE were present in 10 of the 225 brains (4.4%) we examined; half the CTE cases had only a single pathognomonic lesion. Of the 45 brains from decedents who had a history of blast exposure, 3 had CTE, as compared with 7 of 180 brains from those without a history of blast exposure (relative risk, 1.71; 95% confidence interval [CI], 0.46 to 6.37); 3 of 21 brains from decedents with TBI from an injury during military service caused by the head striking a physical object without associated blast exposure (military impact TBI) had CTE, as compared with 7 of 204 without this exposure (relative risk, 4.16; 95% CI, 1.16 to 14.91). All brains with CTE were from decedents who had participated in contact sports; 10 of 60 contact-sports participants had CTE, as compared with 0 of 165 who had not participated in contact sports (point estimate of relative risk not computable; 95% CI, 6.16 to infinity). CTE was present in 8 of 44 brains from decedents with non-sports-related TBI in civilian life, as compared with 2 of 181 brains from those without such exposure in civilian life (relative risk, 16.45; 95% CI, 3.62 to 74.79).Evidence of CTE was infrequently found in a series of brains from military personnel and was usually reflected by minimal neuropathologic changes. Risk ratios for CTE were numerically higher among decedents who had contact-sports exposure and other exposures to TBI in civilian life than among those who had blast exposure or other military TBI, but the small number of CTE cases and wide confidence intervals preclude causal conclusions. (Funded by the Department of Defense-Uniformed Services University Brain Tissue Repository and Neuropathology Program and the Henry M. Jackson Foundation for the Advancement of Military Medicine.).
Clinician utilization of a plasma-only, multiomic minimal residual disease (MRD) assay in 2,000 consecutive patients with colorectal cancer (CRC).
Authors: Katrina Sophia Pedersen, Leslie A. Bucheit, Benjamin R. Tan, Zishuo Ian Hu, Michael Shusterman, Caroline Weipert, Kimberly Banks
Journal: Journal of Clinical Oncology (2022)

e15586 Background: Circulating tumor DNA (ctDNA) for detection of MRD in resected CRC is a prognostic factor for recurrence. However, current utilization of available commercial tests has not been investigated. We report real world clinician use of a validated, plasma-only, multiomic MRD assay (Guardant Reveal) in a large unselected CRC cohort. Methods: Results from Guardant Reveal MRD testing ordered for clinical care in the US were retrospectively queried for the first 2,000 consecutive CRC cases. Pts could be enrolled in a post-operative program to inform adjuvant treatment (PostOP, up to 3 tests within 3-16 weeks post-resection) or a surveillance program (SP) for recurrent tests post-treatment. Pts could have tests across both programs and/or one-time tests. All subsequent tests for the first 2,000 patients were included for analysis (data cut-off: 1/15/2022). Recurrent programs were analyzed for stage (stg) II/III only. Clinical factors were derived from test requisition forms. Results: 2681 tests from 1993 pts were analyzed; 7 pts were excluded due to missing cancer stage. Median age was 64 years (range: 21-65), 55% were male, most (94%) had stg II/III disease (Table). ctDNA was detected in 25% of all pts; detection increased with stage (Table) as expected. Among stg II/III pts, 330 (21%) had only PostOP test/s, 950 (51%) SP only, 54 (3%) had both PostOP and SP; the remainder had one-time test/s outside defined programs. In Stg II/III pts with &gt;1 PostOP test (26%/17% respectively), ctDNA was detected in 102/384 (27%), of whom 72% had it detected on the first test. The median time from surgery to first result was 5 weeks (10 weeks for a second result). 95% of all stg II/III pts had results from PostOP testing before week 12 post-resection. In Stg II/III pts with &gt;1 SP test (47%/54% respectively), ctDNA was detected in 244/1024 (24%), of whom 87% had it detected on a first test. The average time from date of surgery to first surveillance test was 305 days (median: 489, range:51-4618). Conclusions: ctDNA detection rates by a plasma-only multiomic MRD assay in this large CRC clinical cohort are similar to published rates. ctDNA orders by clinicians were most frequent in Stg II/III surveillance settings followed by PostOp, consistent with the population size of eligible patients for PostOp vs. Surveillance use-case. Importantly, nearly all pts tested PostOP had results prior to 12 weeks post-resection, which may inform adjuvant therapy decisions. These findings should be correlated with clinical outcomes to improve the utilization and utility of MRD testing in adjuvant management of CRC. [Table: see text]
Surgical management of challenging renal tumors with imperative indication: The knowledge of anatomy with 3D virtual models drives the decision making
Authors: D. Amparore, A. Pecoraro, F. Piramide, P. Verri, E. Checcucci, S. De Cillis, A. Piana, M. Manfredi, C. Fiori, F. Porpiglia
Journal: European Urology (2022)
Three residues in the BTB domain promote a good partnership between NuRD and Thpok
Authors: Kazuki Okuyama, Ichiro Taniuchi
Journal: Science Immunology (2022)

Among the BTB-ZF transcription factor family, three amino acids in the BTB domain make Thpok unique in repressing cytotoxic lineage-related genes via recruitment of the NuRD chormatin-remodeling complex (see the related Research Article by Gao et al.).
Highlights From Digestive Disease Week—Pandemic-Related Decline in Colorectal Cancer Screening, Lack of Association Between Proton Pump Inhibitors and Dementia, and More
Authors: Rita Rubin
Journal: JAMA (2022)

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A novel glioblastoma prognostic assay using droplet digital polymerase chain reaction.
Authors: Patrick Beck, Kasen Reed Hutchings, Caroline Grant, Kevin Sheng, Joshua Aaron Morales, Robin Varghese, Zhi Sheng
Journal: Journal of Clinical Oncology (2022)

e14026 Background: Glioblastoma (GBM) is an incurable brain tumor for which outcomes have seen little improvement in the past 30 years. Despite limited GBM therapies, accurate prognostic tools can be invaluable in informing best course of treatment. Recently, we have identified the GBM progression gene signature (GBM-PGS), a collection of 31 genes that shows superior accuracy at predicting GBM progression compared to existing biomarkers. From GBM-PGS expression, a GBM progression risk score can be calculated to provide clinicians with patient-tailored prognostic information. However, the question remains as to the best way to measure GBM-PGS to create a clinically applicable test. At our disposal are three approaches to quantify gene expression: quantitative polymerase chain reaction (qPCR), droplet digital PCR (ddPCR), and RNA sequencing (RNA seq). We hypothesize that the combination of high accuracy and sensitivity, while also providing absolute quantification, will deliver ddPCR as the best option for creating a rapid clinical test that is scalable for measuring GBM-PGS. Methods: A ddPCR protocol was developed, and cDNA and primer concentrations were optimized using samples from two GBM cell lines (SF295, LN18). To confirm assay accuracy, GBM-PGS was quantified using ddPCR and compared to GBM-PGS expression by qPCR, a protocol that has previously been thoroughly validated. Finally, GBM-PGS expression was measured in patient tumors using ddPCR, and the GBM-PGS risk score algorithm was trained using an RNA seq data set from the Tissue Cancer Genome Atlas (TCGA). Following training, risk scores were calculated for the patient samples using ddPCR-measured GBM-PGS expression. Risk scores were compared with clinical patient survival to determine if GBM-PGS expression measured by ddPCR could predict patient outcomes. Results: Optimal primer concentration (200 nM) and cDNA concentration (1.2 ng/μl) were identified. GBM-PGS expression measured by ddPCR absolute quantification and qPCR Ct value demonstrated a strong correlation in the SF295 (R 2 = 0.91) and LN18 (R 2 = 0.88) cell lines. GBM-PGS was measured in two patient samples, and the resulting risk scores were calculated as 26.6 and 29.8 (score &gt; 0 = high progression risk; score &lt; 0 = low progression risk) compared to disease free survival times of 12.9 and 10.5 months, respectively, demonstrating an inverse relationship between patient risk score and survival time. Conclusions: Our results demonstrate that we have developed an accurate ddPCR-based assay capable of measuring GBM-PGS in multiple GBM cell lines, and preliminary results suggest that GBM-PGS quantified using ddPCR accurately predicts patient survival.
IMG-14. Cognitive deficits and altered functional network organization in pediatric brain tumor patients
Authors: Benjamin Seitzman, Hari Anandarajah, Alana McMichael, Ally Dworetsky, Rebecca Coalson, Anna Dowling, Timothy Mitchell, Michael Olufawo, Alikem Agamah, Rachel Butler, Catherine Jiang, Hongjie Gu, Donna Dierker, Dennis Barbour, Bradley Schlaggar, Jennifer Strahle, David Limbrick, Joshua Rubin, Joshua Shimony, Stephanie Perkins
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Survivors of pediatric brain tumors experience significant cognitive deficits from their diagnosis and treatment. Mechanisms of cognitive injury are poorly understood, and predictors of long-term outcome are lacking. Large-scale, distributed brain systems provide a window into brain organization and function that may yield insight into these mechanisms and outcomes. Recent evidence suggests that systems-level changes are related to cognitive performance across the lifespan. Here, we evaluated brain network architecture, cognitive performance, and brain-behavior relationships in pediatric brain tumor patients. METHODS: Forty-nine patients (ages 7-18y.o.) with any brain tumor diagnosis underwent resting state functional Magnetic Resonance Imaging (rsfMRI) during regularly scheduled clinical visits. All patients were tested with the NIH Toolbox Cognition Battery. One-hundred thirty-nine age- and sex-matched typically developing children were used as controls. All data were processed to minimize artifactual sources of variance. Functional brain networks were created for each patient via rsfMRI data from 300 regions of interest that sample the whole brain. Multilinear models were implemented to examine brain-behavior relationships, while accounting for demographic and clinical factors. RESULTS: Functional network organization was significantly altered in patients compared to controls (p&amp;lt;0.001). Network organization was more affected in patients who received whole-brain radiation therapy than those who did not (t=2.52, p&amp;lt;0.015). Patients demonstrated significant impairments in multiple domains of cognitive performance, e.g. attention (p&amp;lt;0.0001). Weak relationships were found between cognitive performance and network organization, none of which survived multiple comparison correction. CONCLUSIONS: Brain network architecture is significantly altered in pediatric brain tumor patients. Whole-brain radiation was related to the largest changes. Most network and cognitive changes were significant with large effect sizes, yet brain-behavior relationships were weak. Our results suggest that systems-level changes in brain organization may provide insight into long-term changes in brain function in pediatric brain tumor patients.
EPID-10. Creation, use, and effectiveness of a primary provider education tool for timely pediatric CNS tumor diagnosis based on HeadSmart
Authors: Daniel Pacheco, Claire Fraley, David Walker, Adam Green
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Patients of minority race and ethnicity and lower socioeconomic status experience poorer survival of pediatric CNS tumors in the US. These disparities arise in part from differences in stage of disease at diagnosis, suggesting they could be mitigated by earlier diagnosis. HeadSmart is a campaign in the UK to increase awareness of pediatric CNS tumor symptoms among primary care practitioners and the public that has led to a significant decrease in time to diagnosis. METHODS: We created a 30-minute workshop, based on HeadSmart, to educate primary care providers on the presentation, common symptoms, work-up, and diagnosis of pediatric CNS tumors. We publicized the workshop throughout Colorado and delivered it via live webinar or online video recording. We collected demographic, specialty, and practice setting data from participants via optional survey. Participants could also take a 10-question, multiple-choice assessment of their knowledge on pediatric CNS tumor symptoms, work-up, and diagnosis before and after the workshop. RESULTS: We have now delivered the workshop to more than 400 providers in Colorado and the US. 39 providers participated in the survey; 19 completed both the pre- and post-workshop assessments. The mean pre-workshop score was 4.5 correct out of 10 (range 0-7); the mean post-workshop score was 5.4 (range 3-7) (unpaired t-test p=0.04). The mean improvement was 1.1 (paired t-test p=0.007). The majority of participants who completed the survey were pediatricians (n=30). Family practice (FP) physicians and pediatric/FP advance practice practitioners also participated. There was no significant difference in improvement for pediatricians vs. other providers. CONCLUSIONS: An educational tool based on the HeadSmart campaign was widely disseminated and is effective at increasing understanding of the timely diagnosis of pediatric CNS tumors among primary providers in Colorado. Further study, refinement, and dissemination have the potential to help mitigate disparities in pediatric CNS tumor outcomes.